Alogliptin Gliquitabs^® (Tablets) Instructions for Use

Marketing Authorization Holder

Pharmstandard-Lexredstva OJSC (Russia)

ATC Code

A10BH04 (Alogliptin)

Active Substance

Alogliptin (Rec.INN registered by WHO)

Dosage Forms

	Alogliptin Gliquitabs^®	Film-coated tablets 12.5 mg
		Film-coated tablets 25 mg

Dosage Form, Packaging, and Composition

Film-coated tablets

	1 tab.
Alogliptin	12.5 mg

10 pcs. – blister packs (3 pcs.) – cardboard packs (30 pcs.) – By prescription
14 pcs. – blister packs (2 pcs.) – cardboard packs (28 pcs.) – By prescription
14 pcs. – blister packs (4 pcs.) – cardboard packs (56 pcs.) – By prescription
14 pcs. – blister packs (8 pcs.) – cardboard packs (112 pcs.) – By prescription

Film-coated tablets

	1 tab.
Alogliptin	25 mg

Clinical-Pharmacological Group

Oral hypoglycemic drug

Pharmacotherapeutic Group

Drugs for the treatment of diabetes mellitus; hypoglycemic drugs, other than insulins; dipeptidyl peptidase-4 (DPP-4) inhibitors

Pharmacological Action

Hypoglycemic agent, a highly selective inhibitor of dipeptidyl peptidase-4 (DPP-4). The selectivity of alogliptin for DPP-4 is more than 10,000 times greater than its effect on other related enzymes, including DPP-8 and DPP-9. DPP-4 is the main enzyme involved in the rapid degradation of incretin hormones: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).

Incretin hormones are secreted in the intestine, and their concentration increases in response to food intake. GLP-1 and GIP increase insulin synthesis and its secretion by pancreatic β-cells. GLP-1 also inhibits glucagon secretion and reduces glucose production by the liver. Therefore, by increasing incretin concentrations, Alogliptin increases glucose-dependent insulin secretion and reduces glucagon secretion at elevated blood glucose concentrations. In patients with type 2 diabetes mellitus with hyperglycemia, these changes in insulin and glucagon secretion lead to a decrease in the concentration of glycated hemoglobin HbA_1c and a reduction in plasma glucose concentration, both fasting and postprandial glucose.

Pharmacokinetics

The pharmacokinetics of alogliptin are similar in healthy subjects and in patients with type 2 diabetes mellitus.

The absolute bioavailability of alogliptin is approximately 100%. Concurrent administration with a high-fat meal did not affect the AUC of alogliptin, so it can be taken regardless of food intake. In healthy subjects, after a single oral dose of up to 800 mg of alogliptin, rapid absorption of the drug is observed, with a mean T_max in the range from 1 to 2 hours after administration.

The AUC of alogliptin increases proportionally with a single dose in the therapeutic dose range from 6.25 mg to 100 mg. The coefficient of variability of alogliptin AUC among patients is small (17%). The AUC_(0-inf) of alogliptin after a single dose was similar to the AUC_(0-24) after administration of the same dose once daily for 6 days. This indicates the absence of time dependence in the kinetics of alogliptin after multiple doses.

Plasma protein binding is approximately 20-30%. After a single intravenous administration of alogliptin 12.5 mg in healthy volunteers, the terminal phase V_d was 417 L, indicating that Alogliptin is well distributed in tissues.

No clinically significant accumulation of alogliptin was observed after multiple doses, either in healthy volunteers or in patients with type 2 diabetes mellitus.

Alogliptin does not undergo extensive metabolism; 60 to 70% of alogliptin is excreted unchanged by the kidneys.

After oral administration of ¹⁴C-labeled alogliptin, two main metabolites were identified: N-demethylated Alogliptin, M-I (<1% of the parent substance), and N-acetylated Alogliptin, M-II (<6% of the parent substance). M-I is an active metabolite and a highly selective inhibitor of DPP-4, similar in action to alogliptin itself; M-II does not exhibit inhibitory activity against DPP-4 or other DPP enzymes.

In vivo studies have shown that CYP2D6 and CYP3A4 are involved in the limited metabolism of alogliptin.

In vitro studies also show that Alogliptin does not induce CYP1A2, CYP2C9, CYP2B6 and does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 at concentrations achieved with the recommended alogliptin dose of 25 mg. Under in vitro conditions, Alogliptin may slightly induce CYP3A4, but under in vivo conditions, Alogliptin does not induce CYP3A4.

Alogliptin exists predominantly as the (R)-enantiomer (>99%) and undergoes little or no chiral conversion to the (S)-enantiomer under in vivo conditions. The (S)-enantiomer is not detected when alogliptin is administered at therapeutic doses.

After oral administration of ¹⁴C-labeled alogliptin, 76% of the total radioactivity is excreted by the kidneys and 13% via the intestine. The mean renal clearance of alogliptin (170 mL/min) is greater than the mean GFR (about 120 mL/min), suggesting that Alogliptin is partially eliminated by active renal excretion. The mean terminal T_1/2 is approximately 21 hours.

Indications

Type 2 diabetes mellitus in adults to improve glycemic control when diet and exercise are insufficient: as monotherapy; in combination with other oral hypoglycemic agents or with insulin.

ICD codes

Open the list of ICD codes

ICD-10 code	Indication
E11	Type 2 diabetes mellitus

ICD-11 code	Indication
5A11	Type 2 diabetes mellitus

Dosage Regimen

The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen.

Take orally once daily, with or without food.

The recommended dose for most patients is 25 mg.

Use as monotherapy or as an add-on therapy to metformin, a thiazolidinedione, a sulfonylurea, or insulin.

Use in a triple combination with metformin and a thiazolidinedione or with metformin and insulin.

For patients with moderate renal impairment (creatinine clearance 30 to 50 mL/min), reduce the dose to 12.5 mg once daily.

Contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min) or end-stage renal disease requiring dialysis.

Assess renal function prior to initiation and periodically during treatment.

When used in combination with a sulfonylurea or insulin, consider a dose reduction of the sulfonylurea or insulin to lower the risk of hypoglycemia.

No dose adjustment is required for patients with mild or moderate hepatic impairment.

Contraindicated in patients with severe hepatic impairment.

Available tablet strengths are 12.5 mg and 25 mg.

Do not use in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

Adverse Reactions

Definition of adverse reaction frequency categories: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10,000 and <1/1000), very rare (<1/10,000, including isolated cases), frequency not known (data from post-marketing observations).

Nervous system disorders common – headache.

Gastrointestinal disorders: common – epigastric pain, gastroesophageal reflux disease; frequency not known – acute pancreatitis.

Hepatobiliary disorders: frequency not known – impaired liver function, including hepatic failure.

Skin and subcutaneous tissue disorders common – pruritus, rash; frequency not known – exfoliative skin conditions, including Stevens-Johnson syndrome, angioedema, urticaria.

Respiratory, thoracic and mediastinal disorders: common – upper respiratory tract infections, nasopharyngitis.

Immune system disorders: frequency not known – hypersensitivity reactions, including anaphylactic reaction.

Contraindications

Type 1 diabetes mellitus; diabetic ketoacidosis; chronic heart failure (NYHA class III-IV); severe hepatic impairment (more than 9 points on the Child-Pugh scale); severe renal impairment; pregnancy; lactation (breastfeeding); children and adolescents under 18 years of age; hypersensitivity to alogliptin; history of severe hypersensitivity reactions to any DPP-4 inhibitor, including anaphylactic reactions, anaphylactic shock, and angioedema.

Use in Pregnancy and Lactation

The use of alogliptin is contraindicated during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in severe hepatic impairment (more than 9 points on the Child-Pugh scale).

Use in Renal Impairment

Contraindicated in severe renal impairment.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Special Precautions

Use with caution in patients with a history of acute pancreatitis; in patients with moderate renal impairment; in combination with a sulfonylurea derivative or insulin; as part of a triple combination with metformin and thiazolidinedione.

To reduce the risk of hypoglycemia, it is recommended to reduce the dose of sulfonylurea derivatives, insulin, or the combination of pioglitazone (thiazolidinedione) with metformin when used concomitantly with alogliptin.

Patients with moderate renal impairment require dose adjustment of alogliptin; therefore, it is recommended to assess renal function before starting and periodically during treatment.

The use of DPP-4 inhibitors is associated with a potential risk of developing acute pancreatitis. Patients should be informed about the characteristic symptoms of acute pancreatitis: persistent, severe abdominal pain that may radiate to the back. If acute pancreatitis is suspected, alogliptin should be discontinued and appropriate examination should be performed.

If impaired liver function develops during treatment, the possibility of discontinuing alogliptin therapy should be considered.

Drug Interactions

No clinically significant interaction of alogliptin with other drugs has been observed.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.

Medical Disclaimer